Populations consuming high levels of soy, as in many Asian countries, have lower levels of ovarian hormones, lower rates of breast cancer, and reduced mammographic density than populations consuming typical Western diets. These observations may in part be explained by our clinical studies that found ovarian hormone levels of premenopausal women to be lowest while they were consuming a diet that provided 15% energy from soymilk containing weakly estrogenic isoflavones. No adverse effects were observed. Further questions are whether isoflavones are the critical components influencing breast cancer risk and whether they do so by affecting other reversible risk markers for breast cancer, such as breast density. Women with dense breasts have a 4-6 fold excess risk of developing breast cancer. Moreover, greater breast density makes it more difficult to detect early breast cancer by mammography. To test the hypothesis that consumption of soy isoflavones reduces breast density, we propose a randomized, double blind study, with two arms, and 100 premenopausal women in each arm. Women with >50% of dense breast tissue will be recruited and randomly allocated to take soy isoflavone pills (treatment) or placebo pills containing no isoflavones (control) for 2 years. The daily dose will be 150 mg of total isoflavones. Women will provide blood and urine samples before and during the supplement intervention period for the analyses of ovarian hormones and isoflavones. At baseline and after the intervention period, subjects will be examined for breast density by mammography and magnetic resonance imaging. The efficacy of the intervention will be determined by comparing mean changes of dense breast tissue over the 2-year intervention period in the two groups with adjustment for baseline values and individual patient characteristics of interest. We hypothesize that 1 to 2 years of a soy isoflavone supplement in premenopausal women will reduce the effects of endogenous estrogens and reduce progesterone levels further, which will explain a corresponding decrease in breast density. Our research results will have significant implications for breast cancer risk reduction. Reducing breast density can be expected to reduce the volume of target tissue at risk for breast cancer development and will improve the sensitivity of mammography for screening. The study may lead to a novel, non-invasive and economical approach to breast cancer prevention.